Novel uses for 4-phenylbutyrate (4pba) and its pharmaceutically acceptable salts

Abstract

Novel uses for 4-phenylbutyrate (4PBA) and its pharmaceutically acceptable salts The use of 4PBA in the manufacture of a medicament useful to treat cognitive disorders in dementias coursing with tauopathies is described. The treatment with 4PBA improves cognitive deficit in a classic murine experimental model of Alzheimer's Disease (AD) (Tg 2576) that is accompanied by decreasing levels of a marker characteristic to AD pathologies, such as phosphorylated Tau, and increasing levels in the synthesis of some synaptic plasticity marker proteins such as GluR1 and PSD95. As mediating mechanism for the therapeutic effect we propose a decreasing stress in the endoplasmic reticulum as manifested by increasing levels of the GRP78 protein. On the other hand its inhibiting effect on histone deacetylation and its involvement in chromatin remodeling facilitates protein synthesis processes, which improves synaptic plasticity.

1 - 15 . (canceled) 
     
     
         16 . A method for the prevention or treatment of Alzheimer's disease in a subject in need of said prevention or treatment that comprises administering to the subject a pharmaceutically effective amount of 4PBA or a pharmaceutically acceptable salt thereof. 
     
     
         17 . The method according to  claim 16 , wherein the pharmaceutical acceptable salt of 4PBA is 4PBA sodium salt. 
     
     
         18 . The method according to  claim 16 , wherein 4PBA or its pharmaceutically acceptable salts is administered in combination with a second active ingredient that is an inducer or facilitator agent for clearing brain β-amyloid deposits. 
     
     
         19 . The method according to  claim 18 , wherein the pharmaceutical acceptable salt of 4PBA is 4PBA sodium salt. 
     
     
         20 . The method according to  claim 18 , wherein the brain β-amyloid deposits clearing inducing agent is a metal chelating agent. 
     
     
         21 . The method according to  claim 19 , wherein said metal chelating agent is clioquinol. 
     
     
         22 . The method according to  claim 18 , wherein the brain β-amyloid deposits clearing inducing agent is a catabolizing enzyme. 
     
     
         23 . The method according to  claim 22 , wherein said inducing agent is the IDE insulin degrading enzyme or neprilisin. 
     
     
         24 . The method according to  claim 18 , wherein the brain β-amyloid deposits clearing inducing agent is cerebrolysin. 
     
     
         25 . The method according to  claim 18 , wherein the brain β-amyloid deposits clearing inducing agent are nitrophenols. 
     
     
         26 . The method according to  claim 18 , wherein said nitrophenol is 2,4-dinitrophenol or 3-nitrophenol.